TY - JOUR
T1 - Capped-dose mitomycin C
T2 - A pooled safety analysis from three prospective clinical trials
AU - Ntukidem, Nse
AU - Arce-Lara, Carlos
AU - Otterson, Gregory A.
AU - Kraut, Eric
AU - Cataland, Spero
AU - Bekaii-Saab, Tanios
PY - 2010/1
Y1 - 2010/1
N2 - Background: Mitomycin C (MMC) up-regulates topoisomerase-I and thymidine phosphorylase making it ideal to combine with irinotecan or capecitabine. One of the most devastating toxicities MMC has been associated with is thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) in 4-15% of patients, especially when receiving cumulative doses higher than 60 mg/m 2. Methods: We conducted a pooled safety analysis of 140 patients enrolled in three prospective clinical trials at our institution from 2001 to 2008. MMC on all our studies was capped to a cumulative dose of 36 mg/m 2 to limit toxicity while retaining efficacy. We reviewed our electronic medical records and clinical trial database for individual patient data on these studies with a specific intent to identify patients meeting criteria for TTP/HUS. Results: In combination with irinotecan or capecitabine, MMC was associated with manageable toxicities. We found no cases of MMC-associated TTP/HUS. There were no reported cardiac or pulmonary toxicities in our analysis. Most common grade 3/4 toxicities were diarrhea (19%), neutropenia (17%) and dehydration (12%) predominantly when MMC was combined with irinotecan. Conclusions: In this large pooled analysis, we found MMC, when capped at a cumulative dose of 36 mg/m2, to be safe and tolerable in combination with capecitabine or irinotecan with no reportable cases of TTP/HUS.
AB - Background: Mitomycin C (MMC) up-regulates topoisomerase-I and thymidine phosphorylase making it ideal to combine with irinotecan or capecitabine. One of the most devastating toxicities MMC has been associated with is thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) in 4-15% of patients, especially when receiving cumulative doses higher than 60 mg/m 2. Methods: We conducted a pooled safety analysis of 140 patients enrolled in three prospective clinical trials at our institution from 2001 to 2008. MMC on all our studies was capped to a cumulative dose of 36 mg/m 2 to limit toxicity while retaining efficacy. We reviewed our electronic medical records and clinical trial database for individual patient data on these studies with a specific intent to identify patients meeting criteria for TTP/HUS. Results: In combination with irinotecan or capecitabine, MMC was associated with manageable toxicities. We found no cases of MMC-associated TTP/HUS. There were no reported cardiac or pulmonary toxicities in our analysis. Most common grade 3/4 toxicities were diarrhea (19%), neutropenia (17%) and dehydration (12%) predominantly when MMC was combined with irinotecan. Conclusions: In this large pooled analysis, we found MMC, when capped at a cumulative dose of 36 mg/m2, to be safe and tolerable in combination with capecitabine or irinotecan with no reportable cases of TTP/HUS.
KW - Dose
KW - HUS
KW - Mitomycin C
KW - Thrombotic thrombocytopenic purpura
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U2 - 10.1007/s00280-009-1036-3
DO - 10.1007/s00280-009-1036-3
M3 - Article
C2 - 19506871
AN - SCOPUS:71349086651
SN - 0344-5704
VL - 65
SP - 319
EP - 324
JO - Cancer chemotherapy and pharmacology
JF - Cancer chemotherapy and pharmacology
IS - 2
ER -